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Upin and Ipin are five-year-old Malay twins who live with their elder sister Ros and maternal grandmother Uda (whom they call Opah) in a wooden house in Kampung Durian Runtuh. They have lost their parents in their infancy. Upin and Ipin study in the village's Tadika Mesra (Friendly Kindergarten), where they befriend a motley bunch of classmates, including the adorable and right-thinking Mei Mei, a jocular and poetic Jarjit Singh, the firm but clumsy and short-tempered Ehsan, an easygoing and sarcastic Fizi (Ehsan's cousin), and an entrepreneurial and meticulous Mail.

The headman of Kampung Durian Runtuh is Isnin bin Khamis, better known as Tok Dalang, the wayang kulit champion. Tok Dalang keeps a cluster of rambutan trees for commercial purposes, and a rooster named Rembo. Among the village's other notable residents are Muthu, owner of the village's only food stall who lives with his animal whisperer son Rajoo and pet steer Sapy; Salleh (Sally), a waspish transgender-apparent, who owns a mobile library; and Ah Tong, a strident-voiced vegetable farmer. Kampung Durian Runtuh also invited an Indonesian girl named Susanti who moved in with her family.